Potential roles of Citrulline and watermelon extract on metabolic and inflammatory variables in diabetes mellitus, current evidence and future directions: A systematic review

Abstract

Objective Diabetes mellitus is a prevalent endocrine disorder worldwide. Citrulline is an α‐amino acid, which is abundant in watermelon, and a precursor of arginine and nitric oxide. Decreased bioavailability of nitric oxide is associated with insulin resistance. The present systematic review focused on the existing evidence of citrulline and watermelon extract effects on metabolic and inflammatory parameters in diabetes mellitus. Methods A systematic search of the databases PubMed, Scopus, EMBASE, ProQuest and Google Scholar was conducted for relevant papers published from inception until October 2018. All clinical trials, animal and in vitro studies published in the English language that assessed the role of citrulline and watermelon extract on diabetes mellitus, were eligible. Studies providing inadequate information were excluded. Results Out of 1262 articles we found, only eight articles met the inclusion criteria for analysis. In three studies an increase in the synthesis of nitric oxide was reported with citrulline and watermelon extract supplementation. Four studies showed a significant reduction in blood glucose after supplementation with watermelon extract, and two studies reported a decrease in a number of inflammatory biomarkers following citrulline supplementation. Although citrulline intake caused a significant reduction in HOMA‐IR in one study, inconsistent results were revealed on the effects of citrulline and watermelon extract on insulin levels and lipid profile. Conclusion Citrulline and watermelon extract could improve nitric oxide synthesis, glycaemic status and inflammation in diabetes mellitus. However, further studies are required to shed light on the underlying mechanisms.

Impact of a 3-Month Anti-inflammatory Dietary Intervention Focusing on Watermelon on Body Habitus, Inflammation, and Metabolic Markers: A Pilot Study

“…Watermelon has high levels of several micronutrients including citrulline. [23][24][25] Cell line and animal studies have shown decreases in tumor necrosis factor-alpha and IL-1 beta, which are proinflammatory; whereas, increases in IL-10, which is anti-inflammatory, has been found with administration of this micronutrient. 56,57 Among critically-ill adults, oral citrulline supplementation was found to lower concentrations of proinflammatory cytokines.…”

“…Emphasis was put on watermelon, which is abundant in certain key elements that have been shown to have antiinflammatory properties. [23][24][25] Weekly meal plans were designed to provide participants with 2 meals per day that incorporate watermelon. In each weekly class session, recipes containing watermelon were demonstrated and prepared.…”

“…Previous studies have shown that watermelon or components that are abundant in watermelon (eg, citrulline) have anti-inflammatory effects. [23][24][25] With support from the National Watermelon Promotion Board in the United States, a small pilot study was undertaken to examine the impact of an IMAGINE intervention with heavy focus on watermelon (IMAGINE-Watermelon) on inflammatory markers and body habitus compared to a remotely delivered, information-only control. It should be noted that the intent of this study was to test the effect of an antiinflammatory dietary prescription with heavy incorporation of watermelon recipes on inflammation, not the sole effect of watermelon on inflammation, for reasons described above.…”

Oxidative stress and nitrate/nitrite (NOx) status following citrulline supplementation in type 2 diabetes: a randomised, double‐blind, placebo‐controlled trial

“…Watermelon is a rich source of citrulline, although it contains other bioactive substances such as arginine, pectin and lycopene. Therefore, its antioxidant properties may be related to each or a combination of these compounds ( 37 ) .…”

L-Citrulline: A Non-Essential Amino Acid with Important Roles in Human Health

“…However, You et al [97] reported that chronic Arg (1.5%) or CIT (1.66%) supplementation (in drinking water for 9 weeks) did not prevent or reduce renal injury in a model of type I diabetes in diabetic mice, despite greatly increasing kidney and plasma Arg levels. Finally, a recent systematic review concluded that CIT and watermelon extract may beneficially affect glycemic status and inflammation in diabetes mellitus, although studies on their antioxidant and hypolipidemic effects in diabetic patients are scarce [98].…”